Bone health assessment via digital wrist tomosynthesis in the mammography setting

Bone fractures attributable to osteoporosis are a significant problem. Though preventative treatment options are available for individuals who are at risk of a fracture, a substantial number of these individuals are not identified due to lack of adherence to bone screening recommendations. The issue is further complicated as standard diagnosis of osteoporosis is based on bone mineral density (BMD) derived from dual energy x-ray absorptiometry (DXA), which, while helpful in identifying many at risk, is limited in fully predicting risk of fracture. It is reasonable to expect that bone screening would become more prevalent and efficacious if offered in coordination with digital breast tomosynthesis (DBT) exams, provided that osteoporosis can be assessed using a DBT modality. Therefore, the objective of the current study was to explore the feasibility of using digital tomosynthesis imaging in a mammography setting. To this end, we measured density, cortical thickness and microstructural properties of the wrist bone, correlated these to reference measurements from microcomputed tomography and DXA, demonstrated the application in vivo in a small group of participants, and determined the repeatability of the measurements. We found that measurements from digital wrist tomosynthesis (DWT) imaging with a DBT scanner were highly repeatable ex vivo (error = 0.05%-9.62%) and in vivo (error = 0.06%-10.2%). In ex vivo trials, DWT derived BMDs were strongly correlated with reference measurements (R = 0.841-0.980), as were cortical thickness measured at lateral and medial cortices (R = 0.991 and R = 0.959, respectively) and the majority of microstructural measures (R = 0.736-0.991). The measurements were quick and tolerated by human patients with no discomfort, and appeared to be different between young and old participants in a preliminary comparison. In conclusion, DWT is feasible in a mammography setting, and informative on bone mass, cortical thickness, and microstructural qualities that are known to deteriorate in osteoporosis. To our knowledge, this study represents the first application of DBT for imaging bone. Future clinical studies are needed to further establish the efficacy for diagnosing osteoporosis and predicting risk of fragility fracture using DWT

Practical application of AAPM Report 270 in display quality assurance: A report of Task Group 270

Published in January 2019, AAPM Report 270 provides an update to the recommendations of the AAPM\u27s TG18 report. Report 270 provides new definitions of display types, updated testing patterns, and revised performance standards for the modern, flat-panel displays used as part of medical image acquisition and review. The focus of the AAPM report is on consistent image quality and appearance, and how to establish a quality assurance program to achieve those two goals. This work highlights some of the key takeaways of AAPM Report 270 and makes comparisons with existing recommendations from other references. It also provides guidance for establishing a display quality assurance program for different-sized institutions. Finally, it describes future challenges for display quality assurance and what work remains

Calibrating from Within: Multipoint Internal Calibration of a Quantitative Mass Spectrometric Assay of Serum Methotrexate.

BACKGROUND:Clinical LC-MS/MS assays traditionally require that samples be run in batches with calibration curves in each batch. This approach is inefficient and presents a barrier to random access analysis. We developed an alternative approach called multipoint internal calibration (MPIC) that eliminated the need for batch-mode analysis. METHODS:The new approach used 4 variants of 13C-labeled methotrexate (0.026-10.3 µM) as an internal calibration curve within each sample. One site carried out a comprehensive validation, which included an evaluation of interferences and matrix effects, lower limit of quantification (LLOQ), and 20-day precision. Three sites evaluated assay precision and linearity. MPIC was also compared with traditional LC-MS/MS and an immunoassay. RESULTS:Recovery of spiked analyte was 93%-102%. The LLOQ was validated to be 0.017 µM. Total variability, determined in a 20-day experiment, was 11.5%CV. In a 5-day variability study performed at each site, total imprecision was 3.4 to 16.8%CV. Linearity was validated throughout the calibrator range (r2 > 0.995, slopes = 0.996-1.01). In comparing 40 samples run in each laboratory, the median interlaboratory imprecision was 6.55%CV. MPIC quantification was comparable to both traditional LC-MS/MS and immunoassay (r2 = 0.96-0.98, slopes = 1.04-1.06). Bland-Altman analysis of all comparisons showed biases rarely exceeding 20% when MTX concentrations were >0.4 µM. CONCLUSION:The MPIC method for serum methotrexate quantification was validated in a multisite proof-of-concept study and represents a big step toward random-access LC-MS/MS analysis, which could change the paradigm of mass spectrometry in the clinical laboratory

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Uranium Integral Fission Product Yields for a Spectrally-shaped 14.1 MeV Neutron Source at the National Ignition Facility

This paper describes the experimental results for an energy tuning assembly created to modify the National Ignition Facility deuterium–tritium fusion neutron source into a notional thermonuclear and prompt fission neutron spectrum, which has applications in integral measurements, nuclear data benchmarks, and radiation effects on microelectronics. The Monte Carlo neutron transport utilized MCNP5 to estimate the ETA-modified fluence using the ENDF-B/VIII.0 and IRDFF-II continuous energy nuclear data libraries, and SCALE Sampler was used to estimate the systematic nuclear data covariance using ENDF-B/VII.1 and IRDFF-II in a 252-group structure. The experiment fielded eight activation foils and a highly enriched uranium sample. This provided fifteen reaction channels that were used in a forward-fit comparison to the modeled results and to unfold the neutron spectrum using STAYSL. Gamma-ray spectrometry was performed on the activation and highly enriched uranium foils, and the reduced x2 between the modeled and experimental values was 1.21. The results from the STAYSL unfold, reduced x2 = 1.62, indicated that the modeled neutron spectrum was achieved and the systematic nuclear data uncertainty associated with the neutron transport and activation product cross sections was representative of the experiment. Integral cumulative fission product yield data were collected for 37 mass chains with a combination of gamma-ray spectrometry and radiochemical analysis. Fission product analysis was generally in agreement with two models using a semi-empirical fit and the General Observables of Fission code, with the exception of mass chains 88, 109, 111, 112, 113, 129, 139, 142, 144, 151, and 156

Nuclear Data Covariance Analysis in Radiation-Transport Simulations Utilizing SCALE Sampler and the IRDFF Nuclear Data Library

This article describes the nuclear data covariance analysis of an experimental design for a neutron energy-tuning assembly (ETA) created to shape a 14-MeV neutron point source to an objective spectrum. Underlying nuclear data uncertainties play a large role in the radiation transport and reaction rates for the range of responses to be expected from an experiment. The methodology leveraged the Standardized Computer Analysis for Licensing Evaluation (SCALE) Sampler module to determine the uncertainty in the neutron transport. The reaction uncertainty was perturbed with the International Reactor Dosimetry and Fusion File v.1.05 uncertainty, correlation matrix, and reaction cross section through multivariate normal distribution sampling to provide a final response metric. The resultant neutron fluence uncertainty for the ETA ranged from 2.7% to 6.2% in the energy range from 1.28 keV to 14.1 MeV, which contains 99.99% of the neutron fluence. The integrated uncertainties, including statistical and systematic nuclear data uncertainties, for the reaction products analyzed were 2.33% to 4.84% for most reactions, but 55Mn(n, γ), a less well-characterized reaction occurring in an energy domain with high flux uncertainty, was 19.7%. The mean of the reaction distributions was within 1.1% of the unperturbed nuclear data simulation. The experiment is planned for late 2019, where the predicted results will be compared against the experimental outcomes. The methodology presented can be utilized with alternate nuclear libraries in SCALE to develop uncertainty bounds and neutron flux spectra for many radiation-transport problems

A Dilution Method to Mitigate Biotin Interference in Cardiac Troponin T Testing.

BackgroundOral biotin supplementation is known to interfere with biotin-streptavidin-based immunoassays, including Roche's fifth-generation cardiac troponin T (cTnT) assay, which plays a critical role in the diagnosis of myocardial infarction (MI). The utility of dilution, a quick and easy method to detect and remove interferences, has not been published for biotin interference.MethodsConcentrations of cTnT were measured in pooled serum from clinical samples. Serum samples were supplemented with biotin to known concentrations, then cTnT concentrations were remeasured to assess for biotin interference. Samples were then diluted to assess for effective removal of biotin interference.ResultsAt cTnT values near the critical reporting range for our institution (100 ng/L) we observed significant interference in measured values with added biotin concentrations above 50 ng/mL. In specimens without added biotin, autodilution at a 1:10 ratio yielded a mean 157% capture of measured cTnT, precluding the use of autodilution for detecting and mitigating biotin interference. A 1:10 dilution with serum containing 20-30 ng/L cTnT yielded a mean capture of 107%, which was suitable for detecting underlying biotin interference in supplemented samples.ConclusionsBiotin interference, at supraphysiologic concentrations, may create an artifactual reduction in measured cTnT to levels that could lead to delayed detection of an MI. Dilution with serum of known cTnT concentration of 20-30 ng/L is a fast and effective method to mitigate the analytical consequences of biotin interference